Antineoplastic agents that incorporate platinum complexes attract specialists' attention featuring strong anti-tumor action, which causes violation of the mechanism of malignant cells gene action.
Platinum preparations have a wide range of antineoplastic administration. Cis-dichlorodiammineplatinum (DDP), being the most thoroughly investigated agent of this anti-tumor group of agents, is active against tumors of various origins: spontaneous and inoculated ones, as well as those induced by viruses and chemical carcinogens. The DDP major drawback is connected with its high toxicity, which causes malfunction of kidneys, red marrow and the digestive tract.
A certain antineoplastic agent (A, RU 2086261) is known to contain a platinum complex in the form of cis-diaminodichloro-trans-dihydroxyplatinum (IV) (oxoplatinum) at a rate of 10-25% and sodium bicarbonate and sodium alginete—at respective rates of 25-55% and 40-60%. This agent has been designed for oral administration in pills with the total weight of 0.35-0.60 g each. The therapeutic dose of the agent in question has 20 to 150 mg of platinum content. The medicine is active in treatment of a relatively wide range of malignant diseases and can be characterized by inhibition of metastases growth and zero nephrotoxic properties.
Sodium bicarbonate, a component of the medicinal preparation, acts as a loosening agent with respect to the pill. When it gets into the gastric juice acid medium, the juice undergoes neutralization and carbon dioxide evolves. Gastric juice neutralization prevents substitution of oxoplatinum hydroxyl groups for chloro ligands to be accompanied with tetrachloride generation. Resulting in sodium chloride generation, interaction between hydrochloric acid sodium bicarbonate contributes to stabilization of chlorine ions in cis-diaminodichloro-trans-dihydroxyplatinum (IV).
Selection of sodium alginete as a filling agent is connected with its high binding properties and with the fact that alginic acid generated due to its interaction with hydrochloric acid has good compatibility with living tissues.
Thus, oxoplatinum acts as the only effective antineoplastic substance in the agent under consideration, which accounts for the necessity of relatively high dosage concerning its administration and increases the probability of complications associated with the toxicity of platinum preparations.
In the course of research investigation of various platinum complexes on animals and clinical trials of DDP and some of its analogues a variety of biological features characteristic of platinum complexes were discovered: anti-tumor activity and respective side effects. It has been shown that insignificant changes in the molecular structure of the complex are capable of causing drastic changes in the above features with respect to bioactivity, including anti-tumor activity. Existing relationship between the complex structure and its anti-tumor activity encourages the search for new platinum-containing agents featuring both high activity and low toxicity.